DIETARY METHIONINE UPTAKE BY SPLANCHNIC REGION IN HEALTHY AND SICK CHILDREN

健康儿童和患病儿童内脏区域的膳食蛋氨酸摄取量

• 批准号: 8166704
• 负责人: Leticia Castillo
• 金额: $ 2.67万
• 依托单位: BAYLOR COLLEGE OF MEDICINE
• 依托单位国家: 美国
• 财政年份: 2009
• 资助国家: 美国
• 起止时间: 2009-12-01 至 2010-11-30
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/8166704
• 关键词: Adolescent; Affect; Amino Acids; Area; Arginine; Blood; Blood Circulation; Catabolism; Child; Childhood; Computer Retrieval of Information on Scientific Projects Database; Critical Illness; Cysteine; Data; Diet; Disease; Enteral; Essential Amino Acids; Funding; Glutamine; Grant; Homeostasis; Infant; Infusion procedures; Institution; Intestines; Intravenous; Leucine; Metabolism; Methionine; Newborn Infant; Nutritional; Organ; Pathologic; Patients; Pattern; Play; Population; Process; Protein/Amino Acids Nutrition; Protocols documentation; Research; Research Personnel; Resources; Role; Small Intestines; Source; Sulfur Amino Acids; Tissues; Tracer; United States National Institutes of Health; Venous; cystic fibrosis patients; uptake

This subproject is one of many research subprojects utilizing the resources provided by a Center grant funded by NIH/NCRR. The subproject and investigator (PI) may have received primary funding from another NIH source, and thus could be represented in other CRISP entries. The institution listed is for the Center, which is not necessarily the institution for the investigator. The splanchnic region plays a significant role in the homeostasis of whole body amino acid metabolism and selectively influences the pattern of absorbed amino acids that is subsequently released into the systemic circulation. During critical illness the splanchnic area is profoundly affected, and may influence amino acid metabolism. There are limited data on inter-organ amino acid exchange and the role of splanchnic uptake and catabolism of amino acids in critically ill patients. To determine parenteral and enteral amino acid requirements, it is necessary to determine the extent of the first pass disappearance of amino acids in the splanchnic region. We plan to study a group of healthy adolescents who will serve as controls for our critically ill adolescent group. Sulfur amino acid splanchnic uptake in healthy adolescents has not been determined and needs to be define. Hence enteral requirement of sulfur amino acids in sick children need to be defined. The first objective of this protocol is to conduct studies of methionine and cysteine splanchnic uptake in healthy children adolescents. The studies in healthy children will serve as controls for our critically ill population. We are requesting GCRC support to conduct our studies in the healthy children. We aim to conduct primed, constant simultaneous intravenous and enteral infusions of L-[1-13C] and L[2H2 ]methionine in a first set of studies and of L-[1-13C] and L[2H2 ] cysteine in a second set of studies in healthy children and to use these data to estimate the contribution of splanchnic sequestration to methionine and cysteine requirements. Primary Endpoint: The fraction of methionine or cysteine tracer that disappears in a first-pass through the splanchnic area This protocol is a continuation of our studies on sulfur amino acid metabolism in sick children. We have already conducted studies of methionine splanchnic uptake in critically ill infants, children and adolescents (Please see preliminary data). The splanchnic region plays a significant role in the homeostasis of whole body amino acid metabolism. The splanchnic area selectively influences the pattern of absorbed amino acids that is subsequently released into the systemic circulation. Intestinal amino acid metabolism plays an important role in modulating the entry of absorbed dietary amino acids into the portal circulation. Thus, the pattern of amino acids in the diet differs markedly from that in portal venous blood and does not reflect their availability to extraintestinal tissues. This concept has important implications for protein and amino acid nutrition. The extensive catabolism of dietary essential amino acids in the first pass by the small intestine, a large organ in the body, results in decreased nutritional efficiency. Thus, intestinal amino acid metabolism will influence the utilization efficiency of dietary amino acids and therefore their requirements. Furthermore, it is not known how inter-organ amino acid exchange and splanchnic uptake are affected under pathologic conditions, and how these processes influence amino acid requirements under conditions of disease. There are data on the splanchnic uptake of leucine, arginine, glutamine and methionine in healthy subjects. In the pediatric population there are two studies on leucine splanchnic uptake, in a population of patients with cystic fibrosis and in the newborn period. These studies yield leucine splanchnic uptake values of 24% and 30% respectively. There are no data on methionine and cysteine splanchnic uptake in healthy or sick children. Therefore, the first objective of this proposal is to determine the rates of splanchnic uptake of methionine and cysteine in sick children.

这个子项目是许多研究子项目中的一个 由NIH/NCRR资助的中心赠款提供的资源。子项目和 研究者（PI）可能从另一个NIH来源获得了主要资金， 因此可以在其他CRISP条目中表示。所列机构为 研究中心，而研究中心不一定是研究者所在的机构。 内脏区在机体氨基酸的动态平衡中起着重要作用 酸代谢，并选择性地影响随后释放到体循环中的吸收的氨基酸的模式。在危重病期间，内脏区受到严重影响，并可能影响氨基酸代谢。关于器官间氨基酸交换以及危重患者内脏吸收和氨基酸代谢的作用的数据有限。为了确定肠外和肠内氨基酸的需要量，有必要确定内脏区氨基酸首过消失的程度。我们计划研究一组健康的青少年，他们将作为我们重症青少年组的对照。 健康青少年的含硫氨基酸内脏摄取尚未确定，需要明确。因此，需要确定患病儿童含硫氨基酸的肠内需要量。 本方案的第一个目的是对健康儿童和青少年的蛋氨酸和半胱氨酸内脏摄取进行研究。在健康儿童中进行的研究将作为我们重症人群的对照。我们正在请求GCRC支持我们在健康儿童中进行研究。 我们的目标是在第一组研究中对健康儿童进行L-[1- 13 C]和L[2 H2]蛋氨酸的预充、恒定同时静脉和肠内输注，在第二组研究中对健康儿童进行L-[1- 13 C]和L[2 H2]半胱氨酸的预充、恒定同时静脉和肠内输注，并使用这些数据来估计内脏螯合对蛋氨酸和半胱氨酸需求的贡献。 主要终点：首次通过内脏区域时消失的蛋氨酸或半胱氨酸示踪剂分数 本方案是我们对患病儿童含硫氨基酸代谢研究的继续。我们已经对重症婴儿、儿童和青少年的蛋氨酸内脏摄取进行了研究（请参见初步数据）。 内脏区在机体氨基酸代谢的稳态中起着重要的作用。内脏区选择性地影响随后释放到体循环中的吸收的氨基酸的模式。肠道氨基酸代谢在调节吸收的膳食氨基酸进入门脉循环中起重要作用。因此，饮食中的氨基酸模式与门静脉血中的氨基酸模式明显不同，并且不能反映它们对肠外组织的可用性。这一概念对蛋白质和氨基酸营养具有重要意义。膳食必需氨基酸在第一次通过小肠（人体的一个大器官）时被广泛吸收，导致营养效率降低。因此，肠道氨基酸代谢将影响膳食氨基酸的利用效率，从而影响其需求。此外，还不知道在病理条件下器官间氨基酸交换和内脏摄取如何受到影响，以及这些过程如何影响疾病条件下的氨基酸需求。 有关于健康受试者内脏摄取亮氨酸、精氨酸、谷氨酰胺和甲硫氨酸的数据。在儿科人群中，有两项关于亮氨酸内脏摄取的研究，一项是囊性纤维化患者人群，另一项是新生儿期。这些研究分别产生24%和30%的亮氨酸内脏摄取值。没有关于健康或患病儿童的蛋氨酸和半胱氨酸内脏摄取的数据。因此，本建议的第一个目标是确定患病儿童的蛋氨酸和半胱氨酸的内脏摄取率。